Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans.
Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness. We report here that mutations of LRTOMT are associated with profound nonsyndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, detected by protein blot analyses. LRTOMT2 is a putative methyltransferase. During evolution, new transcripts can arise through partial or complete coalescence of genes. We provide evidence that in the primate lineage LRTOMT evolved from the fusion of two neighboring ancestral genes, which exist as separate genes (Lrrc51 and Tomt) in rodents.
Ahmed
Zubair M
ZM
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA.
Masmoudi
Saber
S
Kalay
Ersan
E
Belyantseva
Inna A
IA
Mosrati
Mohamed Ali
MA
Collin
Rob W J
RW
Riazuddin
Saima
S
Hmani-Aifa
Mounira
M
Venselaar
Hanka
H
Kawar
Mayya N
MN
Tlili
Abdelaziz
A
van der Zwaag
Bert
B
Khan
Shahid Y
SY
Ayadi
Leila
L
Riazuddin
S Amer
SA
Morell
Robert J
RJ
Griffith
Andrew J
AJ
Charfedine
Ilhem
I
Caylan
Refik
R
Oostrik
Jaap
J
Karaguzel
Ahmet
A
Ghorbel
Abdelmonem
A
Riazuddin
Sheikh
S
Friedman
Thomas B
TB
Ayadi
Hammadi
H
Kremer
Hannie
H
D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism; D005190:Family; D008040:Genetic Linkage; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016364:Reading Frames / Q000235:genetics*; D026801:Synteny / Q000235:genetics
C533107:LRTOMT protein, human; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D002334:Carnitine O-Palmitoyltransferase